Meissner Alexander, Jaenisch Rudolf
Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.
Nature. 2006 Jan 12;439(7073):212-5. doi: 10.1038/nature04257. Epub 2005 Oct 16.
The derivation of embryonic stem (ES) cells by nuclear transfer holds great promise for research and therapy but involves the destruction of cloned human blastocysts. Proof of principle experiments have shown that 'customized' ES cells derived by nuclear transfer (NT-ESCs) can be used to correct immunodeficiency in mice. Importantly, the feasibility of the approach has been demonstrated recently in humans, bringing the clinical application of NT-ESCs within reach. Altered nuclear transfer (ANT) has been proposed as a variation of nuclear transfer because it would create abnormal nuclear transfer blastocysts that are inherently unable to implant into the uterus but would be capable of generating customized ES cells. To assess the experimental validity of this concept we have used nuclear transfer to derive mouse blastocysts from donor fibroblasts that carried a short hairpin RNA construct targeting Cdx2. Cloned blastocysts were morphologically abnormal, lacked functional trophoblast and failed to implant into the uterus. However, they efficiently generated pluripotent embryonic stem cells when explanted into culture.
通过核移植获得胚胎干细胞（ES细胞）在研究和治疗方面具有巨大潜力，但这涉及到克隆人类囊胚的破坏。原理验证实验表明，通过核移植获得的“定制化”ES细胞（NT-ESCs）可用于纠正小鼠的免疫缺陷。重要的是，该方法的可行性最近已在人体中得到证明，使得NT-ESCs的临床应用触手可及。已提出改变核移植（ANT）作为核移植的一种变体，因为它会产生异常的核移植囊胚，这些囊胚本质上无法植入子宫，但能够产生定制化的ES细胞。为了评估这一概念的实验有效性，我们使用核移植从携带靶向Cdx2的短发夹RNA构建体的供体成纤维细胞中获得小鼠囊胚。克隆的囊胚在形态上异常，缺乏功能性滋养层，并且无法植入子宫。然而，当将它们植入培养物中时，它们能高效地产生多能胚胎干细胞。
